Gene regulatory networks elucidated from strategic, genome-wide experimental data can aid in the discovery of novel gene function information and expression regulation events from observation of transcriptional regulation events among genes of known and unknown biological function.
Methods designed to elucidate gene regulation pathways have been reported previously (Y. Pilpel et al., Nature Genetics, 29, 153-159, 2001; Friedman et al., J. Comp. Biol., 7, 601, 2000; R. Somogyi et al., Complexity, 1, 45-63, 1996). The inferred networks reported in these studies were derived from gene expression data sets derived from time course, cell cycle and environmental perturbation (P. Spellman et al., Mol. Biol Cell, 9, 3273-3297, 1998; A. P. Gasch, et al., Mol. Cell Biol. 17, 2099-2106, 1997). However, control relationships inferred from such data sets are suspect since they are not based on comprehensive experimental data designed to elucidate transcription-related regulatory control functions. To rigorously and precisely identify novel and complex gene regulatory networks from de novo expression data sets, a systematic and integrated strategy of expression experiments on genomic deletion mutants combined with suitable computational methods is necessary (T. Akutsu et al., J. Comp. Biol., 7, 331, 2000; T. Akutsu et al., Bioinformatics, 16, 727, 2000; M. P. Brown et al., Proc. Natl. Acad. Sci., 97, 262-267, 2000; T. Ideker et al., Science, 292, 929-934, 2001).
Of particular importance in the creation of inferred regulatory networks is the biological relevance of the expression experiments from which the putative control relationships are derived. Genome-wide expression data generated from competitive hybridization disruption experiments offer the advantages of internal control and quantitative measurement of the direct effects of a gene's presence or absence on the expression of other genes. Selection of disruptant experiments to maximize the elucidation of control relationships is valuable for generating useful gene regulatory information.